The transmissible spongiform encephalopathies (TSE's) are neurodegenerative diseases which afflict livestock and humans. These diseases can have a genetic basis, but can also be transmitted by exposure to infected brain tissue. The latter issue represents a significant public health problem. The mechanism of infection resembles many viral diseases, but the infective agent does not seem to be a traditional virus. Thus, the mechanism of TSE transmission may represent a new biological paradigm and it may be relevant to other neurodegenerative diseases, such as Alzheimer's disease. This proposal involves elucidation of the mechanism of TSE transmission at the molecular level. This work will provide important clues as to how to destroy or block the action off the TSE infective agent. In addition, the possibility for human infection by livestock TSE agent will be studied in detail. Finally, the structure of the protein which comprises the infective agent will be modeled.